I will make a detailed study of the cholesterol metabolism of a cell type (the monocyte-macrophage) that is directly involved in the atherosclerotic reaction. The effects on cholesterol metabolism of converting the blood monocyte into a macrophage will be determined. In the rat, I will compare blood monocytes to Kupffer cells and hepatocytes. In humans blood monocytes will be compared to peritoneal macrophages and macrophages taken from breast milk (colostrum). The effects of lipoproteins and hypoxia on the metabolism of the monocyte-macrophage will be studied. I will determine if monocyte-macrophages taken from animals and humans with extensive endothelial injury are different. I will use the monocyte-macrophage in an attempt to define and explain the genetic heterogeneity in familial hypercholesterolemia. Artificial capillaries will be used in order to culture monocyte-macrophages and smooth muscle cells. I will determine if there is an interaction between monocyte-macrophages and other formed elements in the atherosclerotic reaction (smooth muscle cells and platelets).